Abstract: The objective of this Fast Track proposal is to support the development and commercialization of a proprietary positron emission tomography (PET) imaging agent, [68Ga]P16-093, that specifically targets prostate specific membrane antigen (PSMA) in patients with prostate cancer. Prostate cancer is the second leading cause of death from cancer in U.S. men. There are no commercially available 68Ga PSMA inhibitors on the market, which is preventing the widespread use of this clinically useful class of diagnostic drugs. The advantage of targeting PSMA using radiolabeled PSMA inhibitors is the combination of 100x?1000x fold expression levels of PSMA on the epithelium of prostate adenocarcinomas, which in combination with nM affinity constants results in uptake ratios of >50 whereas other radiotracers proposed for PCa exhibit much lower uptake ratios of the order of 5, enabling detection of much smaller lesions. Our [68Ga]P16-093 agent utilizes a proprietary chelator-linker-pharmacophore combination and has performed well in pre-clinical evaluation. Five Eleven Pharma is self-funding two Phase I clinical trials under IND #133222 to determine human dosimetry and pharmacokinetics in cancer patients using [68Ga]P16-093. Preliminary data from these trials has shown a good safety profile, favorable dosimetry and accumulation of [68Ga]P16-093 in PSMA-expressing tissue and prostate cancer lesions. During this early phase development, the FDA has suggested further investigations into the drug substance chemistry to support the longer term development of [68Ga]P16-093 and eventual NDA filing. The Phase 1 study of the Fast Track proposal is designed to validate the manufacturing process of [68Ga]P16- 093 through targeted ?stress? testing, taking into account comments by the FDA addressing the identity, quantitation and stability of isomers in the final drug product. After successful completion of Fast Track Phase I, will have sufficient data to fully characterize the isomer content of the drug substance [68Ga]P16-093, including how isomer content may impact its biological activity. In Phase 2 of the Fast Track SBIR we proposes a Phase IIa clinical study that will focus on PSMA imaging in PCa patients presenting with biochemical recurrence (BCR) ? rising serum PSA after primary treatment. The endpoint of the Phase IIa clinical trial is to detect a 20% change in management care in BCR patients when comparing treatment plans using [68Ga]P16-093 imaging information those based on standard of care imaging alone. This pilot efficacy data will help Five Eleven Pharma to design Phase IIb/III studies that, after consulting with the FDA, will lead to NDA-enabling clinical protocols.